The present invention relates to a porphyrinogen based sensor having selective binding affinity for an explosive chemical. More particularly, this invention is directed to a porphyrinogen derivative possessing cavities which selectively bind the target molecule when the sensor is exposed to environments containing the target molecule. Upon binding of the target molecule, the porphyrinogen derivative undergoes a detectable adsorption and emission of electromagnetic radiation. Moreover, the invention relates to the formation on a metal surface of a self assembled molecular monolayer (SAM) that exposes the porphyrinogen derivative of the present invention to an analyte medium in a manner such that analysis of high sensitivity is obtained.
Chemical sensors must normally fulfill two goals: (1) the development of a specific chemical recognition element that allows a molecule, or class of molecules, to be identified, and (2) a means of signal transduction in which the presence of the molecule causes a measurable change in a physical property of the material. Although these goals are not always separable, the successful design of chemical sensors requires that both is being satisfied. Most transduction approaches are based on optical, resistive, surface acoustic wave, or capacitive measurements. These well-developed methods dominate largely because of their ease of operation, sensitivity, and cost. The chemical recognition elements in these detectors, however, lag far behind.
In a typical sensor fabrication, a solid plastic mass, consisting of the matrix and binder, is prepared which is chemically bound to the polymer/cross-linker matrix and the target molecule. Removal of the target is possible since it is reversibly bound to the binder. The cavity it leaves behind is permanently shaped like the target. Methods for the detection of explosives and explosive residues require complex analytical instruments such as liquid or gas chromatographs coupled with mass spectroscopic or chemiluminescent detection. The associated instrumentation is usually large, expensive, difficult to maintain and requires skilled operators. If laboratory analysis is necessary, extensive documentation is needed for sample transport, increasing the possibility of sample contamination. Immunoassay tests are available for some explosives, but these are cumbersome and have short shelf lives.
A large number of organic pollutants are found in soil. Examples are xenobiotic compounds containing nitro functional groups, which are used in the production of agricultural chemicals, pharmaceuticals, dyes and plastics. Such compounds are also used in mining, farming and they are the main charge in ammunition including landmines. The most common residues contain 2,4,6-trinitrotoluene (TNT), hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX), and associated impurities and environmental transformation products.
Such compounds contaminate their sites of manufacture and storage as well as military installations. In addition, it is estimated that approximately 90% of the mines currently in use are leaking, resulting in the spread of TNT into the soil. Unlike many other pollutants, some of these contaminants have little affinity for soils and rapidly migrate to pollute groundwater. This is a concern as high levels of TNT have been observed to have the potential to inhibit biological activity. Besides the direct consequences of the pollution itself, pollutants of this type may be an indication of the presence of explosives. As landmines are killing and maiming people in former war zones, particularly in remote and poor parts of the world, knowledge of their presence would be of great humanitarian value.
A first requirement in dealing with soil pollution, is an ability to detect polluted sites. Detection systems that are practical and relatively inexpensive are desirable, in order to facilitate their wide-spread use. The currently available detection methods allow for the detection of pollutants, but the methods are both inconvenient and costly.
When referring to information concerning a soil sample each observation relates to a particular location and time. Knowledge of an attribute value, say a pollutant concentration, is thus of little interest unless location and/or time of measurement are known and accounted for in the analysis. The key decisions to achieve cost-effective, accurate site characterizations are the number, location and type of soil samples to be collected, Site characterization errors occur when the sample does not accurately represent the area which the modeling plan assumes it represents. This is a particular problem when the contaminant is distributed non-homogeneously throughout the soil, as occurs with e.g. explosives contamination.
Thus, the characterization of contaminated soils can be expensive and time consuming due to the large number of samples required to effectively evaluate a site.
Present laboratory methods of evaluating environmental samples offer high sensitivity and the ability to evaluate multiple chemicals, but the time and cost associated with such methods often limit their effectiveness. Thus, for many applications there exists a requirement for an economically feasible, robust, and rapid responding system for the mapping of contaminated soils.
Soil contaminated by explosives are traditionally monitored by collecting samples which are analysed in a laboratory by applying various techniques, such as Enzyme Immunoassay and High Performance Liquid Chromatography.
The detection of landmines is normally carried out by sweeping the concerned area using metal-detectors, dogs or manual labour. In military demining, the objective is to clear a minefield as fast as possible using brute force, and usually a clearance rate of 80-90% is accepted. Humanitarian demining, on the other hand, is more difficult and dangerous, as it requires the complete removal of all mines and the return of the cleared minefield to normal use, Today, most humanitarian demining is done using handheld metal detectors finding objects containing metal by utilizing a time varying electromagnetic field to induce eddy-currents in the object, which in turn generates a detectable magnetic field. Old landmines contain metal parts (e.g., the firing pin), but modern landmines contain very small amounts or no metal at all. Increasing the sensitivity of the detector to detect smaller amounts of metal also makes it very sensitive to metal scrap often found in areas where mines may be located. Furthermore, metal detectors, however sophisticated, can only succeed in finding anomalies in the ground without providing information about whether an explosive agent is present or not, One major problem in humanitarian demining is to discriminate between a “dummy” object and a landmine, Identifying and removing a harmless object is a time-consuming and costly process. Dogs have extremely well-developed olifactory senses and can be trained to detect explosives in trace quantities. This technique, however requires extensive training of the dogs and their handlers, and the dog's limited attention span makes it difficult to maintain continuous operations. A number of mine detection techniques are emerging as complements to presently used methods. They include ground penetrating radar (GPR), infrared thermography and advanced metal detectors. A common feature of these techniques is that they detect “anomalies” in the ground but are unable to indicate the presence of an explosive agent. Basically, GPR systems work by emitting a short electromagnetic pulse in the ground through a wideband antenna. Reflections from the ground are then measured to form a vector. The displacement of the antenna allows to build an image by displaying successive vectors side by side. High frequencies are needed to achieve a good spatial resolution, but penetration depth of electric fields being inversely proportional to the frequency, too high frequencies are useless after some centimeters.
Hence, the choice of the frequency range is a trade-off between resolution and penetration depth. Although the detectors can be tuned to be sensitive enough to detect the small amount of metal in modern mines, this is not practically feasible, as it will also lead to the detection of smaller debris and augment the false alarms rate.
WO0177664A2 discloses a so-called molecularly imprinted polymeric explosives sensor. The sensor possesses selective binding affinity for explosives, such as 2,4,6-trinitrotoluene (TNT) and 1,3,5-trinitrobenzene (TNB). The polymeric sensor incorporates a porphyrin unit which undergoes a detectable change in absorption and/or emission of electromagnetic radiation when the polymer is exposed to explosives. However, the document does not disclose the tetra-TTF calix[4]pyrrole used in the present invention.
WO03031953A2 discloses a method and apparatus for sensing nitroaromatics. The subject method can utilize luminescent, for example fluorescent and/or electroluminescent, aryl substituted polyacetylenes and/or other substituted polyacetylenes which are luminescent for sensing nitroaromatics. In a specific embodiment, the subject method utilizes thin films of fluorescent and/or electroluminescent aryl substituted polyactylenes and/or other substituted polyacetylenes which are fluorescent and/or electroluminescent. The document does not disclose the tetra-TTF calix[4]pyrrole used in the present invention.
WO0177650A1 discloses a method for detecting an analyte in a sample, using surface enhanced (resonance) Raman scattering (SE(R)RS) detection, comprising the steps of a) mixing the sample with a reagent such that any analyte present in the sample reacts with the reagent thereby forming a derivatised analyte, wherein the derivatised analyte comprises a chromophore; b) mixing said derivatised analyte with a SE(R)RS active substrate so as to adhere the derivatised analyte thereto; and C) detecting the derivatised analyte by way of SE(R)RS detection whereby any derivatised analyte detected may be correlated with analyte present in the sample. Examples of analytes which may be detected include, aldehydes, amines, explosives, drugs of abuse, therapeutic agents, metabolites and environmental pollutants. The sample may be any suitable preparation in which the target analyte is likely to be found. However, the sample may conveniently be in solution or transferred to a solution before reacting with the reagent. Thus, for example when detecting explosives or drugs of abuse, a sample of air or breath respectively, may be taken and any target analyte absorbed onto a suitable substrate. Thereafter, any target analyte may be removed from the substrate by washing with a suitable solvent, such as dimethylformamide (DMF), acetone or tetrahydrofuran (THF). For example, in the determination of TNT or RDX from the vapour phase, the vapour can first be collected on a suitable material such as tenax and a small amount of solvent washed through the material to produce a small amount of explosive in solution. The preferred solvent for this purpose is dimethylformamide.
WO0026638A1 discloses a sensor for detecting an analyte in a fluid comprising a substrate having a first organic material and a second organic material that has a response to an analyte. The sensor has information storage and processing equipment, and a fluid delivery appliance. This device compares a response from the detector with a stored ideal response to detect the presence of analyte. Methods for use for the above system are described where the first organic material and the second organic material are sensed and the analyte is detected. The method provides for a device, which delivers fluid to the sensor and measures the response of the sensor with the detector. Further, the response is compared to a stored ideal response for the analyte to determine the presence of the analyte. In different embodiments, the fluid measured may be a gas, a liquid, or a fluid extracted from a solid. Eventhough the document mentions the applicability of sensor substrates comprising polymers, such as poly(anilines), poly(thiophenes), and poly(pyrroles), there is no suggestion that the specific tetra-TTF calix[4]pyrrole envisaged by the present invention will be applicable for the sensing of TNT.
US20040234958A1 discloses a method for detecting an analyte in a sample using surface enhanced (resonance) Raman scattering (SE(R)RS) detection, comprising the steps of a) mixing the sample with a reagent such that any analyte present in the sample reacts with the reagent thereby forming a derivatised analyte, wherein the derivatised analyte comprises a chromophore; b) mixing said derivatised analyte with a SE(R)RS active substrate so as to adhere the derivatised analyte thereto; and c) detecting the derivatised analyte by way of SE(R)RS detection whereby any derivatised analyte detected may be correlated with analyte present in the sample.
Considerable effort has been focused on the preparation of supramolecular host systems with the capability of recognizing specific chemical species through weak, noncovalent interactions. The incorporation of redox-active components into host molecules is one means of enhancing the guest recognition process via, for instance, increased donor-acceptor interactions. In this context, the use of tetrathiafulvalene (TTF) appears particularly attractive. To date, a number of TTF-containing systems have been synthesized to study host-guest binding events. However, in almost all cases, only weak interactions were observed with neutral guests.
The present inventors have published a paper (J. AM. CHEM, SOC. 2004, 126, 16296-16297) disclosing one of the porphyrinogen derivatives of the present invention, namely the compound of claim 1, which has been excluded from protection (tetra-TTF calix[4]-pyrrole 2a). However, the prior art known to the inventors does not disclose the use of tetra-TTF calix[4]-pyrrole for the detection of explosives, e.g. by interaction with TNT.
The present inventors have surprisingly found that tetra-TTF calix[4]-pyrrole as well as the porphyrinogen derivatives of the present invention have superior properties with respect to the sensing of explosive chemicals, such as TNT.